Low-intensity transcranial ultrasound stimulation promotes the extinction of fear memory through the BDNF-TrkB signaling pathway

IF 4.5 2区医学 Q1 NEUROIMAGING

NeuroImage Pub Date : 2025-09-01 DOI:10.1016/j.neuroimage.2025.121441

Degong Meng , Cong Zhang , Jiamin Pei , Xiao Zhang , Hanna Lu , Hui Ji , Xiangjian Zhang , Yi Yuan

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引用次数: 0

Abstract

Synaptic plasticity plays a crucial role in the extinction of fearful memories. Low-intensity transcranial ultrasound stimulation (TUS) can modulate synaptic plasticity and promote the extinction of fear memories. However, the mechanism by which TUS promotes the extinction of fear memory remains unclear. This study aimed to explore whether and how synaptic plasticity under TUS is involved in modulating fear memory and the role of the brain-derived neurotrophic factor (BDNF)-the tropomyosin-related kinase B (TrkB) signaling pathway in this process. We used behavioral tests and two-photon fluorescence imaging to investigate the modulatory effects of TUS on fear memory and examined the formation/elimination of dendritic spines and the calcium activity of pyramidal neurons in the prefrontal cortex in mice in vivo. We found that TUS of the prefrontal cortex can promote fear memory extinction in mice while promoting dendritic spine formation, reducing dendritic spine elimination, increasing pyramidal neuron activity, and enhancing the expression of BDNF and its receptor TrkB. Conversely, inhibiting the BDNF-TrkB signaling pathway weakened these effects of ultrasound stimulation. Our study demonstrated that TUS could promote the extinction of fear memories, indicating that TUS has the potential to be used in the clinical treatment of patients with fear memory.

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低强度经颅超声刺激通过BDNF-TrkB信号通路促进恐惧记忆的消退。

突触可塑性在恐惧记忆的消失中起着至关重要的作用。低强度经颅超声刺激可调节突触可塑性，促进恐惧记忆的消退。然而，TUS促进恐惧记忆消失的机制尚不清楚。本研究旨在探讨TUS下突触可塑性是否以及如何参与恐惧记忆的调节，以及脑源性神经营养因子(BDNF)-原肌球蛋白相关激酶B （TrkB）信号通路在这一过程中的作用。采用行为学实验和双光子荧光成像技术研究了TUS对小鼠恐惧记忆的调节作用，并在体内观察了小鼠前额叶皮层树突棘的形成/消除和锥体神经元钙活性的变化。我们发现，前额叶皮层TUS可以促进小鼠恐惧记忆消退，同时促进树突棘形成，减少树突棘消除，增加锥体神经元活性，增强BDNF及其受体TrkB的表达。相反，抑制BDNF-TrkB信号通路会削弱超声刺激的这些作用。我们的研究表明，TUS可以促进恐惧记忆的消退，这表明TUS具有应用于临床治疗恐惧记忆患者的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NeuroImage 医学-核医学

CiteScore

11.30

自引率

10.50%

发文量

809

审稿时长

63 days

期刊介绍： NeuroImage, a Journal of Brain Function provides a vehicle for communicating important advances in acquiring, analyzing, and modelling neuroimaging data and in applying these techniques to the study of structure-function and brain-behavior relationships. Though the emphasis is on the macroscopic level of human brain organization, meso-and microscopic neuroimaging across all species will be considered if informative for understanding the aforementioned relationships.